The FDA approval of new drugs for advanced solid tumors is relying heavily on demonstration of increased survival duration in phase 3 clinical trials. Most trials, however, are not designed to detect differences in quality of life (QOL) or in toxicity levels. A new meta-analysis reviewed pivotal clinical trials that have led to FDA approval of new anticancer drugs focusing on QOL outcomes in 3 areas—treatment-related differences in grade 3 or 4 adverse events (AEs), treatment discontinuation, and toxic deaths (Niraula S, et al. J Clin Oncol. 2012;30:3012-3019).

The increased toxicity was not limited to targeted drugs and applied to new chemotherapeutic agents as well. Indeed, targeted therapies are overall less toxic than chemotherapy; when targeted drugs used as monotherapies were compared with new chemotherapeutic agents, treatment discontinuation and hematologic toxicity rates were lower with the targeted agents. However, because patients in clinical practice are “less selected” than in clinical trials, the likelihood of newer therapy-related toxicity is greater in the real world than in a clinical trial, the investigators suggest. Therefore, they conclude, the use of newer agents and newer chemotherapy must be selective and individualized; oncologists must consider the health status of the individual patient when prescribing therapy with newer agents.